T lymphocytes are essential components of the immune system whose malfunction or absence are central to multiple pathologies, including inborn and acquired immune deficiencies, autoimmunity and cancer. A clinically relevant supply of functional antigen-specific T cells is thus useful for the treatment of a number of disorders, especially in the adoptive cancer immunotherapy setting.
Essential characteristics of adoptively transferred T lymphocytes (as in adoptive immunotherapy) required for the successful eradication of established tumors include their specificity for the tumor, their stimulatory capability, the number of tumor antigen-specific T cells, and their in vivo persistence. Current adoptive T cell therapies are limited by the lack of patient and tumor-specific T cells, including their rarity in the body, their failure to overcome a number of tumor immunoescape mechanisms, and their short life span, especially when using terminally differentiated or “exhausted” effector T cells, i.e. non proliferating T cells even when exposed to specific antigen.
Leukapheresis of patients or allogeneic donors are current sources of T lymphocytes used for adoptive cell therapy. However it is difficult to isolate and expand the typically low numbers of T cells reactive to a desired antigen, i.e. generate antigen-specific functional T cell clones. Furthermore, in some cases peripheral blood lymphocytes are not available, for example from immunodeficient patients.
Therefore, there is a need for therapeutically sufficient and functional antigen-specific T cells for effective use in immunotherapy.